The long range goal of this research is to understand the interactions of solvent and small solutes with the macromolecular matrix that makes up whole tissues. It is clear that at present there is not sufficient information available to make an efficient and direct attack on whole tissues; however, it is also evident that nuclear magnetic resonance will provide a direct and nondestructive method for studying these very complex and heterogeneous systems. The proposed work represents continuing efforts in the study of solvent and solute interactions with macromolecular components of tissues. The approach is directed first at an extensive study of protein crystals because the protein crystal provides the best model for an ordered array of protein molecules for which detailed structural information is available. Although the protein crystals will serve as a model for tissues, the investigation will directly answer several questions concerning the nature of the protein crystal state and the nature of 1) Characterization of the fluidity of both the protein side chains and the solvent in the crystal. 2) Determination of the lifetime of water protein hydration spheres if such exist as a kinetically sensible entity. 3) Quantitative assessment of the precision of currently used protein drying methods. 4) Determination of at least limits for the rates of diffusion of water molecules on protein surfaces. 5) Determination of the state of electrolyte ions in the crystal by direct observation of their nmr spectra in the crystal state. 6) Determination of the extent to which the properties of water change when the volume of water observed decreases to the small sizes often available in tissue systems.